Inclusion body myositis (IBM) is a disease of unknown cause characterized by slowly progressive painless weakness and with no effective treatment. It is one of a group of disorders known as inflammatory myopathies, in which some aspect of autoimmunity is believed to be prominent. IBM has been characterized as a disease in which there is accumulation of abnormal proteins. We propose detailed and large-scale studies of proteins in muscle in IBM and other inflammatory myopathies using powerful protein fractionation and mass spectrometry methods. The specific aims are to look broadly at the profile of proteins present within muscle across the range of inflammatory myopathies;to attempt to purify insoluble protein aggregates from IBM muscle and characterize these aggregates by the use of mass spectrometry;and to correlate proteomic with microarray data. PUBLIC HEALTH RELEVANCE. Diseases of protein aggregation are important public health concerns and this research has the potential to further understand the nature of a disease in which protein aggregation is an important part of the mechanism. The technology developed in this proposal has relevance across a wide range of biomedical research.